The phakomatoses, or ‘neuro-cutaneous disorders’, are a group of three Mendelian autosomal dominantly inherited diseases that present with phenotypes affecting multiple organ systems in affected individuals. Neuro-cutaneous disorders include for example, Neurofibromatosis (NF), Tuberous Sclerosis (TSC) and Von Hippel-Lindau (VHL). These diseases all produce both neurological and dermatological symptoms.
Tuberous sclerosis complex (TSC) is an autosomal dominant tumor-suppressor gene syndrome, characterized by development of distinctive benign tumors (hamartomas) and malformations (hamartias) in multiple organ systems. The brain, skin, heart, and kidneys are commonly affected. TSC lesions occurring in the skin and kidney contain smooth muscle cells, endothelial cells, adipocytes, and large neuronal appearing cells. Despite this complex cellular architecture, kidney and other lesions in TSC appear to be clonal in nature, based on clonality and loss of heterozygosity (LOH) analyses. In the brain, TSC produces both subependymal tubers that line the ventricular sacs and subcortical hamartomas which serve as foci for epileptic discharges. TSC produces cardiac rhabdomyomas in the fetus/newborn that spontaneously regress in the first year of life. TSC is also associated with renal angiomyolipomas, pulmonary symptoms, and manifestations in other organ systems. In addition, TSC is also associated with multiple dermatological features such as hypomelanotic macules, facial angiofibroma, shagreen patches, and ungual fibromas.
A better understanding of the molecular nature of this disease will provide new therapeutic tools to treat the pathologies associated with TSC complex not only in TSC patients but also in non TSC patients afflicted by similar pathologies.